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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 55 records · Page 3Linked to original sources

[GM-CSF.G-CSF].

The basic characteristics of granulo-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) are reviewed. The structure of the proteins and genes have been clarified. The clinical use of these hematopoietic growth factors are also discussed. Diseases for which these growth factors will be effective are follows, the granulocytepenic state after anti-cancer chemotherapy, aplastic anemia, bone marrow transplantation and so on. As these growth factors increase the granulocyte function, these proteins will be effective on the immunodifective state.

Agranulocytosis

Expression of paternal and maternal mitochondrial HSP70 family, hsc74, in preimplantation mouse embryos.

We have investigated the regulation of gene expression of a novel mitochondrial HSP70 family, hsc74 in preimplantation mouse embryos. We used a monoclonal antibody, anti-CSA, which reacts with only one of strain variants of the hsc74. By immunostaining with anti-CSA antibody, the hsc74 protein was constitutively detected in C3H embryos from 1-cell to blastocyst stage, but no signals were detectable in C57BL/6 embryos. To know the timing of paternal genome expression, we examined the expression of hsc74 in (C57BL/6 x C3H)F1 embryos. No positive signals were detectable in embryos before 8-cell stage. In early 8-cell stage weakly positive signals appeared in the peripheral region of the blastomeres. From late 8-cell stage, the protein was intensively detectable and was persistently expressed in all types of cells. We have also applied a sensitive methodology to distinguish genetic variants of hsc74 from C3H and C57BL/6 by reverse transcription polymerase chain reaction followed by single strand conformation polymorphism analysis. In (C57BL/6 x C3H)F1 embryos, the paternal transcripts were first detected in 4-cell embryos, while the maternal transcripts were constantly detectable. These results indicate that the transcripts and proteins of hsc74 were derived only from the maternal gene from 1-cell to 4-cell stages, and that from 4-cell stage the paternal gene is also transcribed, and the significant increase of the paternally derived protein occurred around late 8-cell stage.

Animals

Molecular forms of human brain natriuretic peptide (BNP) in plasma of patients on hemodialysis (HD).

Plasma brain natriuretic peptide (BNP) levels have been reported to increase in patients with heart failure and end-stage renal disease (ESRD); however, little is known about molecular forms of plasma BNP that increase in these diseases. In the present study, we analyzed the molecular forms of plasma BNP in ESRD patients of both before (pre-) and after (post-) hemodialysis (HD) state. The plasma extract was analyzed by gel filtration on a TSK-GEL G2000 SW column followed by a RIA for both BNP and atrial natriuretic peptide (ANP). In the pre-HD patients, a 14- to 2300-fold increase in plasma level of immunoreactive (ir-) BNP was observed when compared to normal controls. A ratio of BNP-32 to g-BNP (pro BNP) in plasma from the patients was much larger than that in plasma from normal subjects, indicating that the high plasma level of ir-BNP level in the patients on HD largely results from a marked increase in BNP-32. HD significantly (P < 0.01) lowered the plasma levels of both BNP-32 and g-BNP with a greater reduction in BNP-32 than in g-BNP. Whereas, a-ANP was a main molecular form of plasma ANP in both pre- and post-HD plasma. These results suggest that plasma BNP-32 plays an important role in the sodium-fluid balance and that secretion and metabolism of BNP may differ from those of ANP in the HD patients.

Adult

[A case of localized fibrous tumor of the pleura with bloody pleural effusion].

A 25-year-old female came to our hospital with the chief complaint of right dorsal pain. On her initial chest X-ray, the tumor (5 x 3 cm) was recognized in the right lower lung field. The tumor grew rapidly during the three month period between the initial X-ray taken on her first visit and her getting admitted in the hospital. A preoperative diagnosis was done by percutaneous aspiration biopsy. Initial diagnosis of spindle cell tumor was made. Partial resection of right lower lobe with chest wall resection was carried out. There were about 500 ml of bloody pleural effusion. Macroscopically, the tumor was encapsulated, measuring 8.0 x 6.0 x 5.0 cm. The cross section was of a yellowish brown solid tumor. The histological diagnosis was of a low grade malignant fibrous mesothelioma. Only 14 cases of localized mesothelioma with pleural effusion including our case have been reported in Japan. She is still alive nine months after surgery. This patient should be carefully followed for the recurrence of the disease.

Adult

[General pharmacology of T-3761, a new oral quinolone antibacterial agent (1). Effect on the central nervous system].

General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the central nervous system were investigated in laboratory animals. The results obtained are summarized as follows. 1. T-3761 exerted no significant effects on spontaneous motor activity, motor coordination, pentobarbital-induced hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice at oral doses of 100, 300 and 1,000 mg/kg. The same oral doses of T-3761 exerted no significant effects on body temperature and passive avoidance response in rats. 2. T-3761 had no effects on EEG in cats and spinal reflex in rats at intravenous doses of 10, 30 and 100 mg/kg. 3. Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4. An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4-biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen also did not induce convulsions in mice. 5. T-3761 did not inhibit GABA receptor binding in rat brain synaptic membranes at 10(-4) M in either the absence or presence of BPAA. These results suggest that T-3761 is an antibacterial agent which would be unlikely to produce any side effects on the central nervous system and to produce convulsion when combined with NSAIDs in clinical use.

Animals

[General pharmacology of T-3761, a new oral quinolone antibacterial agent (2). Effect on the respiratory and cardiovascular systems, autonomic nervous system and other functions].

General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the respiratory and cardiovascular systems, autonomic nervous system and other functions were investigated in laboratory animals. The results obtained are summarized as follows. 1. Respiratory and cardiovascular systems: Oral administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious rats. But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an increase in respiratory rate, induced hypotension, caused increase or decrease in heart rate and altered ECG patterns (elevation of T waves and reduction of voltage of QRS complexes, etc.) in anesthetized dogs. Intravenous administration of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease, hypertension, heart rate decrease and ECG patterns changes (T waves elevation and extrasystole) in anesthetized rabbits. 2. Autonomic nervous system and smooth muscle organs: T-3761 increased the epinephrine-induced contraction of the isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml. T-3761 decreased the acetylcholine-induced contraction of the isolated guinea pig ileum and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at concentration of 10(-4) g/ml. T-3761 increased the norepinephrine-induced contraction of the isolated rabbit thoracic aorta at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight mydriasis in mice. 3. Digestive system: T-3761 decreased the spontaneous motilities of isolated ileum and colon at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and intestinal transit time in rats or mice. 4. Renal functions: Oral administration of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP excretion in rats. 5. Hematological examinations: T-3761 showed no effects on resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at concentration of 10(-6)-10(-4) g/ml. Oral administration of T-3761 at dose of 100-1,000 mg/kg did not affect bleeding time or blood glucose level in rats. 6. Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100 mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized rats. Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight augmentation of carrageenin-induced hind paw edema in rats. From these results, it can be assumed that T-3761 had a wide safety margin as an oral antibacterial agent.

Animals

[Studies on SY5555 in the field of pediatrics].

SY5555, a new oral penem, in the form of dry syrup (powder which is dissolved before use) was evaluated for its pharmacokinetics and clinical efficacy in pediatric patients. Oral administration of 5 mg/kg and 10 mg/kg of SY5555 in dry syrup resulted in respective maximum plasma concentrations of 1.08 +/- 0.38 micrograms/ml (n = 4) and 2.50 +/- 1.81 micrograms/ml (n = 4), half-lives (T 1/2) of 2.72 +/- 1.86 hours (n = 3) and 1.14 +/- 0.88 hours (n = 4), and urinary excretion until 6 hours of 4.7% (n = 1) and 3.86 +/- 2.01% (n = 4). Clinical efficacy was evaluable in 22 patients, and the overall efficacy rate was 100%. As for bacteriological efficacy, all 5 strains of pathogenic organisms identified were eradicated (eradication rate, 100%). No remarkable adverse reactions or abnormal laboratory values were observed.

Administration, Oral

[Diagnostic value of tissue polypeptide antigen in pleural effusions with malignant pleural mesothelioma].

There are no known tumor makers of malignant pleural mesothelioma. We measured the concentration of TPA in the pleural effusions from patients with malignant pleural mesothelioma and from patients with other pleural diseases, evaluate its clinical usefulness. The concentration of TPA was more than 7,000 U/l (mean: 18,600 +/- 9,867 U/l, n = 5) in all patients with malignant pleural mesothelioma, but it was less than 4,000 U/l in those with benign asbestos pleurisy and other benign pleural effusion (benign asbestos pleurisy 1,598 +/- 570, n = 5: p < 0.01, tuberculous pleurisy 1.37 +/- 759, n = 11: p < 0.01, others 2,497 +/- 2,152 n = 3: p < 0.05). The concentration of TPA in the pleural effusions was not significantly different between malignant pleural mesothelioma and lung cancer (12,287 +/- 17,070 U/l). However, in all patients with lung cancer and high TPA concentrations, cytologically malignant cells were detected in the pleural effusions. TPA was high in all five patients with malignant pleural mesothelioma, but cytologically malignant cells were detected in only one patient. Only in malignant pleural mesothelioma (not in other benign disease or in lung cancer) was the concentration of TPA more than 4,000 U/l, and no evidence of malignancy was obtained by cytological methods. These findings suggest that assessing TPA in the pleural effusion might contribute to the diagnosis of malignant pleural mesothelioma.

Adult

Mechanism of histamine-induced calcium efflux from cultured bovine adrenal chromaffin cells: possible involvement of an Na+/Ca2+ exchange mechanism.

The effect of stimulation of the histamine receptor on Ca2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Histamine (10(-5) M) increased the intracellular free Ca2+ ([Ca2+]i) to a peak in the presence or absence of extracellular Ca2+, followed by decrease with time. Histamine (10(-8)-10(-5) M) also stimulated 45Ca2+ efflux from cultured bovine adrenal chromaffin cells in a concentration dependent manner. Its stimulatory effect on 45Ca2+ efflux was inhibited by the specific histamine H1 receptor antagonist mepyramine. The increase in histamine-stimulated 45Ca2+ efflux was inhibited by deprivation of extracellular Na+ and by the Na+/Ca2+ exchange inhibitor amiloride. In addition, histamine stimulated 22Na+ influx into the cells, and this action was inhibited by amiloride. These results suggest that stimulation of the histamine H1 receptor regulates Na+/Ca2+ exchange in cultured bovine adrenal chromaffin cells.

Adrenal Medulla

GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly enhances serine phosphorylation of epidermal growth factor receptor, independently of receptor-receptor interaction.

GM3 ganglioside (II3NeuAcLacCer) inhibits epidermal growth factor (EGF)-dependent receptor autophosphorylation and cell growth (Bremer, E.G., Schlessinger, J., and Hakomori, S. (1986) J. Biol. Chem. 261, 2434-2440), whereas de-N-acetyl-GM3 (deNAcGM3; II3NeuNH2Lac-Cer) promotes these processes (Hanai, N., Dohi, T., Nores, G. A., and Hakomori, S. (1988) J. Biol. Chem. 263, 6296-6301). Receptor-receptor interaction has been proposed as an essential initial mechanism for EGF-dependent activation of EGF receptor kinase (EGF-RK) (Schlessinger, J. (1988) Trends Biochem. Sci. 13, 443-447). We studied the effects of GM3 and deNAcGM3 on EGF-RK function and EGF-R dimerization, and observed that (i) EGF-dependent in vitro and in vivo (in situ) phosphorylation of A431 cells at both monomeric and dimeric forms of EGF-R was inhibited in a dose-dependent manner by GM3, but unaffected by GM1. (ii) Quantities of both forms of EGF-R remained constant regardless of addition of various quantities of GM3 or GM1, as revealed by blotting with antibodies directed to the C-terminal region of EGF-R, or by cell surface 125I-labeling followed by immunoprecipitation. (iii) DeNacGM3 in the absence as well as in the presence of a minimal quantity of detergent significantly enhanced EGF-R phosphorylation, particularly Ser phosphorylation. (iv) DeNAcGM3 was detected in a large variety of actively growing tumor cells. Findings i and ii above indicate that GM3 directly inhibits EGF-dependent Tyr phosphorylation but does not affect receptor-receptor interaction. Findings iii and iv suggest that deNAcGM3 strongly promotes serine phosphorylation (in addition to Tyr phosphorylation) of EGF-R and may function as a second messenger in the process of cell growth stimulation.

Animals

Pre-operative estimation of complete resection for patients with oesophageal carcinoma.

Three hundred and seventy-nine patients were studied retrospectively regarding the possibility of a complete resection of the oesophageal carcinoma based on the combined findings of pre-operative oesophagogoraphy and computed tomography (CT). One hundred and four out of 129 patients (96.1%) having lesions which did not demonstrate all three of the aforementioned factors (a lesion shorter than 8 cm, a normal oesophageal axis, and normal contact of the lesion with neighboring organs in CT) underwent a complete resection of the oesophageal lesion. Fifty-three percent of the patients (52/97) with a lesion showing only one of these factors had a complete resection. Whereas, on the other hand, a complete removal of the malignancy was only possible in 22% of the patients with two or all three of the findings. Moreover, as a result of further analysis limited for resected cases, the number of positive factors in these pre-operative findings correlated with the advancement of the surgical stage, which reflected a curability in surgery and a rate of postoperative complications. In order to make adequate plans for the treatment of patients with advanced oesophageal cancer, the finding of (i) the length of lesion, (ii) a deep ulceration and deformity of the oesophageal axis and (iii) any abnormal contact in CT, are considered to be very useful.

Adult

Gold dermatitis due to ear piercing: correlations between gold and mercury hypersensitivities.

A case of allergic contact dermatitis due to gold pierced earrings is reported. The patient developed recurring redness and swelling on her earlobes a month after the wearing of pierced-type gold earrings, which was followed by the appearance of reddish nodules around the puncture marks. Patch tests revealed positive reactions to 0.1% mercuric chloride, 1% gold sodium thiomalate and 0.2% chloroauric acid. We also demonstrated that guinea pigs contact-sensitized with a mercuric compound developed positive patch test reactions to both mercuric and gold compounds. These results suggest that there may be correlations between gold and mercury hypersensitivities.

Adult

[Crystalloids in salivary gland pleomorphic adenoma].

We examined crystalloids in salivary gland pleomorphic adenomas. The crystalloids were detected in 4 of 34 pleomorphic adenomas (11.7%). In three cases they were found in the minor salivary gland and in one case in the major salivary gland. Light microscopy revealed that all the crystalloids were in parenchyma. They were composed of eosinphilic structure and radially arranged clusters of needle-shape fibers. The central parts sometimes contained clear space. They were usually closely surrounded by neoplastic myoepithelial cells. All 4 cases containing crystalloids were million reaction-negative and positive to van Gieson, Mallory and Reticulin Silver Impregnation stains. Therefore all the crystalloids in our 4 cases were considered as collagen-rich.

Adenoma, Pleomorphic

Molecular cloning and biological activities of rat adrenomedullin, a hypotensive peptide.

Adrenomedullin is a new hypotensive peptide recently identified in human pheochromocytoma arising from adrenal medulla. We report here the cDNA encoding a rat adrenomedullin precursor. The precursor is 185 amino acids in length, including a 21 residue putative signal peptide at the N-terminus. Rat adrenomedullin consists of 50 amino acids similar to, but distinct from human adrenomedullin; 2 residues were deleted and 6 residues were substituted compared to those in the human peptide. In the proadrenomedullin N-terminal 20 peptide, whose amino acid sequence is present in adrenomedullin precursor, 3 amino acids were substituted. RNA blot analysis showed that rat adrenomedullin mRNA was expressed in adrenal glands, lung, kidney, heart, spleen, duodenum and submandibular glands. Synthetic rat adrenomedullin elicits a potent and long-lasting hypotensive activity in anesthetized rats.

Adrenal Glands